Post on 08-Aug-2020
CERVICAL CANCER SCREENING SCENARIOS
for pan-Canadian Cervical Screening Initiative
June 18 2014
Acknowledgements
• Anthony Miller
• Cathy Popadiuk
• Claude Nadeau
• Keiko Asakawa
• Marc Brisson
• Michael Wolfson
• Saima Memon
• Steve Gribble
• William Flanagan
• Zenia Ferreira
2
Objectives
• Target setting: incidence rate
• What will the incidence rate be in the future if we continue with the status quo?
• What would the incidence rate be if we increased screening participation to 80%? Altered our screening programs? Introduced primary HPV DNA testing?
• If we switch to primary HPV DNA testing:
• What are the health outcomes?
• How much will it cost?
• Is it cost-effective in Canada compared to cytology?
3
4
Assumptions
Screening Inputs Baseline assumptions
Recruitment period 2015 onward
Recruitment age for PAP screening 21-69 years old (25, 30-69)
Interval years between initial rescreen 3 (5, 10)
Screening participation 70%
Screening modalities Pap or HPV DNA test
5
Vaccination Inputs Baseline assumptions
Age 12
Sex Female
Vaccine deployment year 2007
Vaccine type Quadrivalent
Vaccination coverage 70% (50%, 90%)
Proportion protected 100%
Degree of protection 100%
0
1
2
3
4
5
6
7
8
9
10
2014 2019 2024 2029 2034 2039 2044 2049
Inci
de
nce
pe
r 1
00
,00
0Incidence per 100,000
Triennial PAP 21-69: 70% ppt: No vacc
6
STATUS QUO
*non-age-standardized
0
1
2
3
4
5
6
7
8
9
10
2014 2019 2024 2029 2034 2039 2044 2049
Inci
de
nce
pe
r 1
00
,00
0Incidence per 100,000
Triennial PAP 21-69: 70% ppt: No vacc
Triennial PAP 21-69: 70% ppt (70%V)
7
*non-age-standardized
STATUS QUO + vaccination
2037
0
2
4
6
8
10
12
14
16
18
20
Inci
de
nce
(p
er 1
00
,00
0)
Incidence of cervical cancer in 2037
8
*non-age-standardized
No vaccine, no screening
Vaccine, no screening
5.8 5.9 6.0 7.1 7.4 9.2 13.2 17.3
If unspecified, age = 21-69 and interval = x 3 years
9
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
2014 2019 2024 2029 2034 2039 2044 2049
Mo
rtal
ity
pe
r 1
00
,00
0Mortality per 100,000
Triennial PAP 21-69: 70% ppt: No vacc
*non-age-standardized
STATUS QUO
10
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
2014 2019 2024 2029 2034 2039 2044 2049
Mo
rtal
ity
pe
r 1
00
,00
0Mortality per 100,000
Triennial PAP 21-69: 70% ppt: No vacc
Triennial PAP 21-69: 70% ppt: (70%V)
STATUS QUO + vaccination
*non-age-standardized
11
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
2014 2019 2024 2029 2034 2039 2044 2049
Mo
rtal
ity
pe
r 1
00
,00
0Mortality per 100,000
Triennial PAP 21-69: 70% ppt: No vacc
Triennial PAP 21-69: 70% ppt: (70%V)
Triennial PAP 21-69: 70% ppt (90% V)
*non-age-standardized
Herd immunity
12
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0M
ort
alit
y (p
er 1
00
,00
0)
Mortality per 100,000 in 2037
Triennial PAP 21-69: 70% ppt (70%V) Triennial PAP 25-69: 70%ppt (70% V) Triennial PAP 30-69: 70% ppt (70% V)
Triennial PAP 21-69: 80% ppt: No vacc PAP 21-69 every 5 yrs: 70% ppt: (70%V) Triennial PAP 21-69: 70% ppt: No vacc
PAP 21-69 every 10 years: 70% ppt (70%V) No screening: 70%V No vaccination or screening
If unspecified, age = 21-69 and interval = x 3 years
2.8 3.0 3.12.5 2.6 2.6 6.55.43.9
Vaccine, no Pap
No vaccine, no Pap
Incremental Cost-Effectiveness Ratios (ICERs)
13
reject(dominated)
consider(more expensive but
saves more lives)
consider(less expensive but saves fewer lives)
accept(dominant)
Co
sts
Lives
14
No vaccine, screen x 3, 21-69
Vaccine, screen x 3, 21-69Vaccine, screen x 5 years
Vaccine, screen x 10
Vaccine, screen 25-69
Vaccine, screen 30-69
Vaccine, no screening
No vaccine, no screening
998,000
998,100
998,200
998,300
998,400
998,500
998,600
$0 $5 $10 $15 $20 $25 $30 $35 $40
Tota
l QA
LYs
Tho
usa
nd
s
Total CostsBillions
Cost-Effectiveness*
*3% discount rate
Cost-effectiveness ratios*
Total Cost (in '000,000's)
Total QALYs(in '000's)
ICER
No vaccine, no screening $12,016 998,016 -
Vaccine, no screening $11,840 998,253 DOMINANT
Vaccine, cytology 21-69 x 10 years $19,811 998,390 $ 21,000
Vaccine, cytology 21-69 x 5 years $25,421 998,448 $ 31,000
Vaccine, cytology 30-69 x 3 years $29,867 998,482 $ 38,000
Vaccine, cytology 25-69 x 3 years $31,438 998,488 $ 41,000
Vaccine, cytology 21-69 x 3 years $33,027 998,491 $ 44,000
No vaccine, cytology 21-69 x 3 years $35,572 998,383 $ 64,000
15*3% discount rate applied
16
$0.0 $0.5 $1.0
Triennial PAP 21-69: 70% ppt: No vacc
Triennial PAP 21-69: 70% ppt (90% V)
Triennial PAP 21-69: 70% ppt (50%V)
Triennial PAP 21-69: 70% ppt (70%V)
Triennial PAP 25-69: 70%ppt (70% V)
Triennial PAP 30-69: 70% ppt (70% V)
PAP 21-69 every 5 yrs: 70% ppt: (70%V)
PAP 21-69 every 10 years: 70% ppt (70%V)
No screening: 70%V
No vaccination or screening
BillionsAverage annual cost (2015-2025)
Cost of HPV vaccinationScreening costCost non-cancer treatment (excluding warts)Cost of treating wartsCost of cancer treatment
17
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
3,000,000
3,500,000
Screening cytology count
Average annual screening cytology count (2015-2025)
PAP 21-69 every 10 years:70% ppt (70%V)PAP 21-69 every 5 yrs: 70%ppt: (70%V)Triennial PAP 30-69: 70% ppt(70% V)Triennial PAP 25-69: 70%ppt(70% V)Triennial PAP 21-69: 70% ppt:No vaccTriennial PAP 21-69: 70% ppt(50%V)Triennial PAP 21-69: 70% ppt(70%V)Triennial PAP 21-69: 70% ppt(90% V)
18
0
50,000
100,000
150,000
200,000
250,000
300,000
Colopscopy count
Average annual colopscopy count (2015-2025)
No vaccination or screening
No screening: 70%V
PAP 21-69 every 10 years: 70%ppt (70%V)
PAP 21-69 every 5 yrs: 70% ppt:(70%V)
Triennial PAP 30-69: 70% ppt(70% V)
Triennial PAP 25-69: 70%ppt(70% V)
Triennial PAP 21-69: 70% ppt(90% V)
Triennial PAP 21-69: 70% ppt(70%V)
Triennial PAP 21-69: 70% ppt(50%V)
Triennial PAP 21-69: 70% ppt:No vacc
19
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
2014 2019 2024 2029 2034 2039 2044 2049
Mo
rtal
ity
pe
r 1
00
,00
0
Mortality per 100,000
HPV DNA 30-69 every 5 years (70%V)
HPV DNA 25-69 every 5 years (70%V)
*non-age-standardized
No difference in mortality*Not comparable to cytology
results, but comparable to each other
Considerations
• Due to little empirical data on sexual behaviour, long-term data on vaccine efficacy, and existing questions around the development and progression of lesions and HPV-related cancers, higher degree of parameter uncertainty
• Uncertainty around future performance of cytology due to reduced prevalence
• Due to very low prevalence of cervical cancer, estimates are subject to higher degree of Monte Carlo uncertainty
20
Conclusions
• By 2037, an incidence of 6 per 100,000 is projected, assuming that screening programs remains unchanged (70% cytology x 3 years in 21-69).
• Increasing the start age of screening to 25 or 30 has little impact on cervical cancer incidence or mortality and generates cost-savings.
• Increasing the screening interval to every 5 or 10 years is more cost-effective, however is associated with increased mortality.
21
Next Steps
•Primary HPV DNA testing• 21-29 :cytology, 30-69 HPV• 21-34: cytology, 35-69 HPV• HPV only with cytology triage
•Different screening strategies in vaccinated vs unvaccinated cohorts
•Vaccinating boys
•Oropharyngeal, vulvar, vaginal and anal cancers
•Vaccine effectiveness or longevity
22
https://cancerview.ca/cancerriskmanagement
Natalie Fitzgerald, Program Manager, Economics, Cancer Risk Management Platform
natalie.fitzgerald@partnershipagainstcancer.ca
416-619-5780
23
24
Appendix
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
Nu
mb
er
of
infe
cte
d f
em
ale
sPrevalence of HPV 16/18
No vaccination
70% vaccinated
25
POP (lifetime)
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
Nu
mb
er
of
infe
cte
d f
em
ale
sPrevalence of HPV 16/18
No vaccination
50% vaccinated
70% vaccinated
90% vaccinated
26
POP (lifetime)
0
2
4
6
8
10
12
14
16
18
20
Inci
de
nce
(p
er 1
00
,00
0)
Incidence of cervical cancer in 2037with varying vaccination rates
5.5
27
5.8 6.3
0
1
2
3
4
5
6
7
Mo
rtal
ity
(per
10
0,0
00
)
2037 PAP Mortality Rate Triennial PAP 21-69: 70%ppt (90% V)Triennial PAP 21-69: 70%ppt (70%V)Triennial PAP 25-69:70%ppt (70% V)Triennial PAP 21-69: 70%ppt (50%V)Triennial PAP 30-69: 70%ppt (70% V)Triennial PAP 21-69: 80%ppt: No vaccPAP 21-69 every 5 yrs: 70%ppt: (70%V)Triennial PAP 21-69: 70%ppt: No vacc
28
*non-age-standardized
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
Mo
rtal
ity
(per
10
0,0
00
)Mortality per 100,000 in 2037
29
*non-age-standardized
2.4 2.5 2.6 2.6 2.8 3.0 3.12.5 2.6 2.6
30
997.7997.8997.9998.0998.1998.2998.3998.4998.5998.6
$0
$5
$10
$15
$20
$25
$30
$35
$40
Mill
ion
s
Bill
ion
s
Lifetime cost and QALYLifetime cost
* 3% discount
31Murphy et al., Cervical screening: a guideline for clinical practice in Ontario. J Obstet Gynaecol Can, 2012 May; 34(5): 453-8.
Cost of screening test
Cytology HPV DNA test
Family physician visit $67.82 $67.82
Tray fee $10.99 $10.99
Lab cost - tech $3.12 $3.12
Lab cost - pathologist $93.24 $93.24
Test n/a $85.67
Total $175.17 $260.85
32
33
Parameter: Cervical cancer screening and pre-cancer treatment costs
Types of test and treatment in HPV cervical cancer screening
Cytology (PAP) screen
Cytology (PAP)
re-assessment
Initial colposc
opy (withou
t biopsy)
Re-assessment
colposcopy
within 6
months (withou
t biopsy)
Re-assessment
colposcopy not within
6 months (withou
t biopsy)
Biopsy HPV test
when recent (<=6
months) liquid sample already exists
HPV test
when recent (<=6
months) liquid sample
does not
exist
Observation (do
nothing)
Cold knife
Leep Cryo Laser Hysterectomy
Warts remova
l
Base case scenario (default)
175.17 141.05 955.71 724 656.23 102.71 260.85 260.85 0 1851.23
1887.19
1887.19
1887.19
3068.01
190
34
Parameter: Sensitivity and specificity of cytology
Cytology type - Conventional cytology
Scenario - Base case scenario (default)
Cytology result
All cells normal
Atypical squamous cells of
undetermined significance (ASC-US)
Atypical squamous cells, maybe high
grade lesion (ASC-H)
Low grade squamous intra-epithelial lesion
(CIN1)
High grade squamous intra-epithelial lesion (CIN2 or CIN3)
Atypical glandular cells
(AGC)Adenocarcinoma
in situ (AIS)Has cervical
cancer
Progression status
No infection and no lesion97 1.5 0.2 1 0.25 0 0 0.05
Infected but no lesion97 1.5 0.28 1 0.17 0 0 0.05
Warts 97 1.5 0.28 1 0.17 0 0 0.05
CIN1 41 12 2.83 29 15.17 0 0 0
CIN2 20 5 4.14 20 48.86 0 0 2
CIN3 20 5 2.65 20 50.35 0 0 2
Adenocarcinoma in situ (AIS)
131.86 9.74 2.26 9 84 26.4756 58.5244 5
Cervical cancer
0 6 0.44 9 53.56 0 0 31
35
Parameter: Sensitivity and specificity of colposcopy
Scenario - Base case scenario (default)
Colposcopy results
Less than LSIL LSIL
CIN2 or CIN3: lesion satisfactory
and visible
CIN2 or CIN3: lesion not
satisfactory AIS Cervical CancerProgression status
No infection and no lesion 88 7 3 2 0 0
Infected but no lesion88 7 3 2 0 0
Warts 88 7 3 2 0 0CIN1 22 62 15 1 0 0CIN2 8 10 47 35 0 0CIN3 8 10 18 64 0 0Adenocarcinoma in situ (AIS) 0 0 0 0 1 0Cervical cancer 0 0 0 0 0 1
36
Parameter: Sensitivity and specificity of HPV DNA test
Scenario - Base case scenario (default)
Progression status
No infection and no lesion
Infected but no lesion Warts CIN1 CIN2 CIN3
Adenocarcinoma in situ (AIS)
Cervical cancer
HPV_INFECTION
Not infected with HPV
0 0 0 0 0 0 0 0
Infected with HPV 1 1 1 1 1 1 1 1
37
TREATMENT PATHWAYS
38
39
40
41
42
43
44
45
46